The role of complement and/or neutrophils in mediating tissue injury in ischemic myocardium will be studied utilizing a non-human primate (baboon) model. Experimental myocardial infarction will be induced by coronary artery ligation in four groups of baboons: 1) normal; 2) C3-depleted; and 4) C3-and neutrophil-depleted. Uniplolar epicardial electrocardiographic (ECG) mapping of the free left ventricular wall will be performed 15-120 minutes following ligation to define unequivocal areas of ischemia (greater than 2 mV ST segment elevation), intermediate or marginal areas (less than 2 mV ST segment elevation or ST-T segment depression); and normal myocardium (isoelectric ST segments). Six baboons for each group will be sacrificed 24, 48, 72 hours and 7 days later and the temporal sarcolemmal complement localization (Clq, C4, C3, Factor B, and C5b-9) will be determined quantitatively (% of cells involved) in the three areas of myocardium previously defined by the epicardial ECG mapping. These data will be correlated with the degree of neutrophilic and mononuclear infiltration in the affected areas and with extent of myocadial necrosis determined histologically by light and electron microscopy and biochemically by myocardial creatine kinase depletion. Mechanisms for the antibody-independent activation of complement will be studied in vitro utilizing sarcolemmal, mitochondrial and sacroplasmic reticular membranes isolated from normal baboon heart. Activation and/or binding of various complement components will be quantitated on normal heart membranes and by membranes altered by a variety of hydrolytic enzymes and chemical treatments. Attempts will be made to establish a myocardial tissue or organ culture model in order to determine whether in vitro induction of ischemia and/or substart deprivation leads to membrane alterations that alter the activation and binding of complement. The proposed studies will attempt to document the role of complement in mediating cellular injury in ischemic myocardium and the evolution of infarct size. By defining the mechanisms for complement activation and tissue injury, we hope to develop appropriate interventions to block complement dependent myocardial tissue injury.